Qiu Chunyan, Zhang Yue, Chen Longhua
Department of Radiation Oncology, Nanfang Hospital, Southern Medical University, Guangzhou, China.
Department of Radiation Oncology, First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
Iran J Public Health. 2020 Jan;49(1):56-67.
Risk of colorectal cancer (CRC) is defined by genetic predisposition and environmental factors that often co-occur and interact, resulting in diversiform biological reactions. The present study attempted to investigate transcriptome alteration and adaptation associated with CRC progression.
The study consisted of patients who presented at Memorial Sloan-Kettering Cancer Center, Guangzhou, China with a colonic neoplasm in 1992-2004. Microarray GSE41258 of the study was acquired from Gene Expression Omnibus and 253 included microarrays were categorized by groups of normal colon, early primary tumor, lymph node metastases primary tumor, advanced primary tumor and distant metastases. Short Time-series Expression Miner (STEM) was applied to discover tumor grade-dependent gene expression patterns. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were carried out to explore functional enrichment of differential expression genes (DEGs).
Overall, 2870 significant DEGs were screened out on all groups. Six significant grade-dependent gene expression patterns were statistically significant. DEGs in all significant patterns were mainly assembled in GO terms of metastases and deterioration of tumor, epithelial proteins and cytokines, and protein binding and bridging. DEGs in profile 0 down-regulated with higher tumor grade, prominently enriched in KEGG pathways of metabolism.
Besides many well-known colorectal cancer-related pathways, DEGs of profiles especially those down-regulated with CRC progression, clustered in various metabolic pathways including starch and sucrose metabolism, fatty acid metabolism, nitrogen metabolism, as well as xenobiotics biotransformation that link to tumorigenesis, demonstrating the impairment of physiological metabolic pathways in the context of tumor progression. These results gave a high potential for therapeutic strategies.
结直肠癌（CRC）风险由遗传易感性和环境因素共同决定，这些因素常同时出现并相互作用，导致多样的生物学反应。本研究试图探究与CRC进展相关的转录组改变和适应性变化。
该研究纳入了1992年至2004年在中国广州纪念斯隆 - 凯特琳癌症中心就诊的结肠肿瘤患者。研究的微阵列GSE41258数据来自基因表达综合数据库（Gene Expression Omnibus），253个纳入的微阵列按正常结肠、早期原发性肿瘤、淋巴结转移原发性肿瘤、晚期原发性肿瘤和远处转移分组。应用短时序列表达挖掘工具（Short Time-series Expression Miner，STEM）发现肿瘤分级依赖性基因表达模式。进行基因本体论（Gene Ontology，GO）和京都基因与基因组百科全书（Kyoto Encyclopedia of Genes and Genomes，KEGG）分析以探索差异表达基因（DEGs）的功能富集情况。
总体而言，在所有组中筛选出2870个显著的DEGs。六种显著的分级依赖性基因表达模式具有统计学意义。所有显著模式中的DEGs主要集中在GO术语中的肿瘤转移和恶化、上皮蛋白和细胞因子以及蛋白质结合和桥接方面。模式0中的DEGs随肿瘤分级升高而下调，在KEGG代谢途径中显著富集。
除了许多众所周知的与结直肠癌相关的途径外，特别是那些随CRC进展而下调的模式中的DEGs，聚集在各种代谢途径中，包括淀粉和蔗糖代谢、脂肪酸代谢、氮代谢以及与肿瘤发生相关的外源性物质生物转化，这表明在肿瘤进展过程中生理代谢途径受到损害。这些结果为治疗策略提供了很大的潜力。
